Organic compounds are typically synthesized by reactions in which a starting material or reactant is contacted with one or more other reactants, reagents, or catalysts to form a new organic product. The separation of the desired products from any added reactants, reagents or catalysts (and/or from any byproducts derived from such reaction components) can be tedious and time consuming. Accordingly, improved methods for the separation of organic reaction products from other reaction components are needed.
Along these lines, the use of fluorous reagents, reactants and catalysts has recently begun to offer attractive new options. The use of such fluorous techniques is illustrated in general terms in FIG. 1. An organic (non-fluorous) starting material or reactant is contacted with a fluorous reactant, reagent or catalyst, possibly with other non-fluorous reaction components, and typically in a solvent, to form a new organic product or mixture of products. The organic product(s) are then separated from the unreacted fluorous reactant, reagent or catalyst and any other fluorous byproducts derived therefrom by simple fluorous-organic phase separation techniques such as liquid-liquid separation and/or solid-liquid separation. Such techniques have been described, for example, in U.S. Pat. Nos. 5,777,121 and 5,859,247, the disclosures of which are incorporated herein by reference.
Organotin reactants, reagents and catalysts are a powerful class of molecules that effect many useful transformations of organic starting materials or reactants to organic products. Accordingly, the use of organotin compounds is common practice in organic synthesis. See, for example, Davies, A. G. Organotin Chemistry; VCH: Weinheim, pp 327 (1997) and Chemistry of Tin; 2nd ed.; Smith, P. J., Ed.; Blackie: London, pp 578 (1997). However, the separation of the newly formed, non-tin containing organic products from the remaining tin compounds in the reaction mixture is notoriously difficult and improvements in separation techniques are needed to unlock the potential power of organic reactions mediated by organotin compounds.
Many of the most popular types of organotin reagents have the formula R3SnX, where R is an alkyl group, often butyl, and X is a group which is involved in the reaction with an organic substrate. A few among many possible examples of such compounds include BU3SnH, Bu3SnN3, Bu3SnCl and Bu3SnPh. Recently, fluorous analogs of these compounds have been introduced. The fluorous analogs are generally designed to accomplish reactions similar to the corresponding non-fluorous compound but to facilitate separation after reaction. In currently available fluorous tin reagents, each of the three alkyl groups R is replaced by a spacer group Rs attached to a fluorous group Rf according to the following general formula: [(Rf)Rs)]3SnX. Examples of such fluorous tin reagents include (C6F13CH2CH2)3SnH, (C6F13CH2CH2)3SnN3, (C6F13CH2CH2)3SnCl, (C6F13CH2CH2)3SnPh, etc.
Illustrative examples of the uses of one of these fluorous tin reagents, (C6F13CH2CH2)3SnH, are shown in FIG. 2. Reduction of adamantyl bromide with 1 equiv of (C6F13CH2CH2)3SnH followed by fluorous-organic liquid-liquid extraction provides the organic product adamantane on evaporation of the organic liquid phase and the fluorous product (C6F13CH2CH2)3SnBr on evaporation of the fluorous phase. A similar reduction can be conducted in a more economical way by using a catalytic amount of the fluorous tin hydride along with an inexpensive inorganic reductant like sodium cyanoborohydride. A three-phase liquid extraction then provides the respective products: inorganic salts (from the aqueous phase), adamantane (from the organic phase), and the tin hydride catalyst (from the fluorous phase).
While currently available fluorous tin reagents provide advantages over the traditional (non-fluorous) trialkyltin class of reagents, some disadvantages remain that restrict the broad application thereof. For example, existing reagents with three fluorous chains can have low solubility in organic solvents. This low solubility can lead to problems in selecting suitable reaction solvents since it is often desirable that the tin compounds have substantial solubility under the reaction conditions. For example, the reactions in FIG. 2 require a non-standard solvent or co-solvent such as benzotrifluoride. Moreover, the large numbers of fluorines in currently available fluorous tin reagents result in compounds of high molecular weight, which is a detraction from the standpoint of expense and atom economy. Finally, certain classes of organotin reagents, for example Bu2SnO, have fewer than three alkyl chains and cannot be rendered fluorous by current strategies.
It is thus very desirable to develop fluorous reaction compounds or components that substantially reduce or eliminate such problems.